tbuckley/cabot-search huggingface dataset:
Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction
Authors: Michael Molitor, Maria T Bayo-Jimenez, Omar Hahad, Claudius Witzler, Stefanie Finger, Venkata S Garlapati, Sanela Rajlic, Tanja Knopp, Tabea K Bieler, Melania Aluia, Johannes Wild, Jeremy Lagrange, Recha Blessing, Steffen Rapp, Andreas Schulz, Hartmut Kleinert, Susanne Karbach, Sebastian Steven, Wolfram Ruf, Philipp Wild, Andreas Daiber, Thomas Münzel, Philip Wenzel
Journal: Cardiovascular Research (2023)

Traffic noise may play an important role in the development and deterioration of ischaemic heart disease. Thus, we sought to determine the mechanisms of cardiovascular dysfunction and inflammation induced by aircraft noise in a mouse model of myocardial infarction (MI) and in humans with incident MI.C57BL/6J mice were exposed to noise alone (average sound pressure level 72 dB; peak level 85 dB) for up to 4 days, resulting in pro-inflammatory aortic gene expression in the myeloid cell adhesion/diapedesis pathways. The noise alone promoted adhesion and infiltration of inflammatory myeloid cells in vascular/cardiac tissue, paralleled by an increased percentage of leucocytes with a pro-inflammatory, reactive oxygen species (ROS)-producing phenotype and augmented expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase type 2 (Nox2)/phosphorylation of nuclear factor 'kappa light chain enhancer' of activated B-cells (phospho-NFκB) in peripheral blood. Ligation of the left anterior descending artery resulted in worsening of cardiac function, pronounced cardiac infiltration of CD11b+ myeloid cells and Ly6Chigh monocytes, and induction of interleukin (IL) 6, IL-1β, CCL-2, and Nox2, being aggravated by noise exposure prior to MI. MI induced stronger endothelial dysfunction and more pronounced increases in vascular ROS in animals preconditioned with noise. Participants of the population-based Gutenberg Health Cohort Study (median follow-up:11.4 years) with incident MI revealed elevated C-reactive protein at baseline and worse left ventricular ejection fraction (LVEF) after MI in case of a history of noise exposure and subsequent annoyance development.Aircraft noise exposure before MI substantially amplifies subsequent cardiovascular inflammation and aggravates ischaemic heart failure, facilitated by a pro-inflammatory vascular conditioning. Our translational results suggest that measures to reduce environmental noise exposure will be helpful in improving the clinical outcome of subjects with MI.Key questionKey finding Take-home-MessageAircraft noise exposure before MI substantially amplifies cardiovascular inflammation and aggravates cardiac impairment after MI.
Impact of Ultra High-risk Genetics on Real-world Outcomes of Transplant-eligible Multiple Myeloma Patients
Authors: Aikaterini Panopoulou, Sandra Easdale, Mark Ethell, Emma Nicholson, Mike Potter, Asterios Giotas, Helena Woods, Tracy Thornton, Charlotte Pawlyn, Kevin D. Boyd, Martin F. Kaiser
Journal: HemaSphere (2023)

Refined prediction of early relapse following standard-of-care (SoC) autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) could inform real-world risk-stratified post-ASCT strategies. We investigated the impact of double hit genetics (≥2 adverse markers: t(4;14), t(14;16), t(14;20), gain(1q), del(17p)) on outcome in 139 NDMM patients who underwent SoC ASCT between January 2014 and October 2019 at our center. Double hit genetics were associated with a significantly shortened progression-free survival (hazard ratio [HR] = 4.27, P &lt; 0.001) and overall survival (HR = 4.01, P = 0.03), and characterized most early relapses. Our results support the real-world utility of extended genetic profiling for improved risk prediction in NDMM.
DNA-PK hyperactivation occurs in deletion 11q chronic lymphocytic leukemia and is both a biomarker and therapeutic target for drug-resistant disease
Authors: Sara E. F. Kost, Ali Saleh, Shek H. Yuan, Bozena Kuzio, Spencer B. Gibson, Lin Yang, Versha Banerji, James B. Johnston, Sachin Katyal
Journal: Blood Cancer Journal (2023)

DNA-PK hyperactivation occurs
Waning humoral and cellular immunity after COVID-19 vaccination in patients with psoriasis treated with methotrexate and biologics: a cohort study
Authors: Amanda Kvist-Hansen, Laura Pérez-Alós, Rownaq Fares Al-Sofi, Line Dam Heftdal, Sebastian Rask Hamm, Dina Leth Møller, Mia Marie Pries-Heje, Kamille Fogh, Cecilie Bo Hansen, Rasmus Bo Hasselbalch, Johannes Roth Madsen, Jose Juan Almagro Armenteros, Ruth Frikke-Schmidt, Linda Hilsted, Erik Sørensen, Sisse Rye Ostrowski, Henning Bundgaard, Susanne Dam Nielsen, Kasper Iversen, Claus Zachariae, Peter Garred, Lone Skov
Journal: British Journal of Dermatology (2023)

mRNA-based COVID-19 vaccines have short- and long-term efficacy in healthy individuals, but their efficacy in patients with psoriasis receiving immunomodulatory therapy is less studied.To investigate long-term immunity after COVID-19 vaccination in patients with psoriasis receiving immunomodulatory therapy.A prospective cohort study including patients (n = 123) with psoriasis receiving methotrexate (MTX) or biologics and controls (n = 226). Only mRNA-based COVID-19 vaccines administered with standard intervals between doses were investigated. Markers of immunity included SARS-CoV-2 spike glycoprotein-specific IgG and IgA, neutralizing capacity, and interferon-γ release from T cells stimulated with peptides of the SARS-CoV-2 spike glycoprotein.The proportion of IgG responders was lower 6 months after vaccination in patients receiving anti-tumour necrosis factor (TNF) treatment compared with controls. Anti-TNF treatment was associated with lower IgG levels (β = -0.82, 95% confidence interval -1.38 to -0.25; P = 0.001). The median neutralizing index was lower in the anti-TNF group [50% inhibition (interquartile range [IQR] 37-89)] compared with controls [98% inhibition (IQR 96-99)]; P < 0.001. Cellular responses were numerically lowest in the anti-TNF group.Treatment with anti-TNF has an impact on the immunity elicited by mRNA-based COVID-19 vaccination in patients with psoriasis, resulting in a faster waning of humoral and cellular markers of immunity; however, the clinical implications are unknown.
Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
Authors: Burak Yulug, Ozlem Altay, Xiangyu Li, Lutfu Hanoglu, Seyda Cankaya, Simon Lam, Halil Aziz Velioglu, Hong Yang, Ebru Coskun, Ezgi Idil, Rahim Nogaylar, Ahmet Ozsimsek, Cemil Bayram, Ismail Bolat, Sena Oner, Ozlem Ozdemir Tozlu, Mehmet Enes Arslan, Ahmet Hacimuftuoglu, Serkan Yildirim, Muhammad Arif, Saeed Shoaie, Cheng Zhang, Jens Nielsen, Hasan Turkez, Jan Borén, Mathias Uhlén, Adil Mardinoglu
Journal: Translational Neurodegeneration (2023)

Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.
The Kidney Failure Risk Equation: Evaluation of Novel Input Variables including eGFR Estimated Using the CKD-EPI 2021 Equation in 59 Cohorts
Authors: Morgan E. Grams, Nigel J. Brunskill, Shoshana H. Ballew, Yingying Sang, Josef Coresh, Kunihiro Matsushita, Aditya Surapaneni, Samira Bell, Juan J. Carrero, Gabriel Chodick, Marie Evans, Hiddo J.L. Heerspink, Lesley A. Inker, Kunitoshi Iseki, Philip A. Kalra, H. Lester Kirchner, Brian J. Lee, Adeera Levin, Rupert W. Major, James Medcalf, Girish N. Nadkarni, David M.J. Naimark, Ana C. Ricardo, Simon Sawhney, Manish M. Sood, Natalie Staplin, Nikita Stempniewicz, Benedicte Stengel, Keiichi Sumida, Jamie P. Traynor, Jan van den Brand, Chi-Pang Wen, Mark Woodward, Jae Won Yang, Angela Yee-Moon Wang, Navdeep Tangri
Journal: Journal of the American Society of Nephrology (2023)

The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities.
Digital mental health for postpartum women: perils, pitfalls, and promise
Authors: Natalie Feldman, Sarah Perret
Journal: npj Digital Medicine (2023)

Postpartum mental health conditions are a public health concern, affecting a large number of reproductive-age women and their families. Postpartum depression alone affects at least 14% of new mothers and their families. However, very little has been written about how advances in digital mental health can benefit women in the postpartum period, or how those advances may poorly serve this vulnerable population. This manuscript takes a high-level view of the advances in different areas of digital mental health, including telehealth, apps, and digital phenotyping. In this comment, we explore ways in which digital interventions for postpartum mental health may help with connection to treatment, accessibility, agency, and ease of access. We also note particular concerns for how digital postpartum mental health may encounter issues of low-quality resources, ethical considerations, and equity considerations. We provide suggestions for how to leverage the promise and avoid the pitfalls of digital mental health for postpartum women.
Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy
Authors: Yao Liu, Zhenzhen Xun, Kun Ma, Shuhang Liang, Xianying Li, Shuo Zhou, Linmao Sun, Yufeng Liu, Yanhua Du, Xinyu Guo, Tianming Cui, Huanran Zhou, Jizhou Wang, Dalong Yin, Ruipeng Song, Shugeng Zhang, Wei Cai, Fanzheng Meng, Hongrui Guo, Bo Zhang, Di Yang, Rujuan Bao, Qingsong Hu, Jiabei Wang, Youqiong Ye, Lianxin Liu
Journal: Journal of Hepatology (2023)
Regulation of Photosensitivity by the Hippo Pathway in Lupus Skin
Authors: Grace A. Hile, Patrick Coit, Bin Xu, Amanda M. Victory, Mehrnaz Gharaee‐Kermani, Shannon N. Estadt, Mitra P. Maz, Jacob W. S. Martens, Rachael Wasikowski, Craig Dobry, Lam C. Tsoi, Ramiro Iglesias‐Bartolome, Celine C. Berthier, Allison C. Billi, Johann E. Gudjonsson, Amr H. Sawalha, J. Michelle Kahlenberg
Journal: Arthritis & Rheumatology (2023)

Objective Photosensitivity is one of the most common manifestations of systemic lupus erythematosus (SLE), yet its pathogenesis is not well understood. The normal‐appearing epidermis of patients with SLE exhibits increased ultraviolet B (UVB)–driven cell death that persists in cell culture. Here, we investigated the role of epigenetic modification and Hippo signaling in enhanced UVB‐induced apoptosis seen in SLE keratinocytes. Methods We analyzed DNA methylation in cultured keratinocytes from SLE patients compared to keratinocytes from healthy controls (n = 6/group). Protein expression was validated in cultured keratinocytes using immunoblotting and immunofluorescence. An immortalized keratinocyte line overexpressing WWC1 was generated via lentiviral vector. WWC1‐driven changes were inhibited using a large tumor suppressor kinase 1/2 (LATS1/2) inhibitor (TRULI) and small interfering RNA (siRNA). The interaction between the Yes‐associated protein (YAP) and the transcriptional enhancer associate domain (TEAD) was inhibited by overexpression of an N/TERT cell line expressing a tetracycline‐inducible green fluorescent protein–tagged protein that inhibits YAP–TEAD binding (TEADi). Apoptosis was assessed using cleaved caspase 3/7 and TUNEL staining. Results Hippo signaling was the top differentially methylated pathway in SLE versus control keratinocytes. SLE keratinocytes (n = 6) showed significant hypomethylation (Δβ = −0.153) and thus overexpression of the Hippo regulator WWC1 ( P = 0.002). WWC1 overexpression increased LATS1/2 kinase activation, leading to YAP cytoplasmic retention and altered proapoptotic transcription in SLE keratinocytes. Accordingly, UVB‐mediated apoptosis in keratinocytes could be enhanced by WWC1 overexpression or YAP–TEAD inhibition, mimicking SLE keratinocytes. Importantly, inhibition of LATS1/2 with either the chemical inhibitor TRULI or siRNA effectively eliminated enhanced UVB‐apoptosis in SLE keratinocytes. Conclusion Our work unravels a novel driver of photosensitivity in SLE: overactive Hippo signaling in SLE keratinocytes restricts YAP transcriptional activity, leading to shifts that promote UVB apoptosis. image
Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection
Authors: Chrispin Chaguza, Anne M. Hahn, Mary E. Petrone, Shuntai Zhou, David Ferguson, Mallery I. Breban, Kien Pham, Mario A. Peña-Hernández, Christopher Castaldi, Verity Hill, Kendall Billig, Rebecca Earnest, Joseph R. Fauver, Chaney C. Kalinch, Nicholas Kerantzas, Tobias R. Koch, Bony De Kumar, Marie L. Landry, Isabel M. Ott, David Peaper, Irina R. Tikhonova, Chantal B.F. Vogels, Wade Schulz, Ronald I. Swanstrom, Scott C. Roberts, Nathan D. Grubaugh
Journal: Cell Reports Medicine (2023)

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.
Evolution of Magnetic Resonance Imaging Lesions at the Sacroiliac Joints During and After Pregnancy by Serial Magnetic Resonance Imaging From Gestational Week Twenty to Twelve Months Postpartum
Authors: Rosa Marie Kiil, Ulrich Weber, Anne Gitte Loft, Rikke Damkjær Maimburg, Anne Grethe Jurik
Journal: Arthritis & Rheumatology (2023)

Sacroiliac (SI) joint magnetic resonance imaging (MRI) findings simulating sacroiliitis related to axial spondyloarthritis (SpA) may occur in women before and after birth. This study was undertaken to explore the prevalence, evolution, and topography of SI joint MRI lesions in pregnant and postpartum women.A prospective cohort study included 103 first-time mothers who underwent up to 5 serial SI joint MRI between gestational week 20 and 12 months postpartum. After calibration, 3 assessors independently evaluated bone marrow edema (BME), including sacroiliitis according to the Assessment of SpondyloArthritis international Society (ASAS), as well as structural lesions, using the Spondyloarthritis Research Consortium of Canada (SPARCC) and a novel 2-plane assessment method.BME was frequent both during pregnancy and the postpartum period, peaking at 3 months postpartum with a prevalence of 69% (SPARCC) and 80% (2-plane method), but still present in 54% (SPARCC) and 58% (2-plane method) of subjects at 12 months postpartum. At 12 months postpartum, sacroiliitis according to the current ASAS definition was met in 41%, while 21% and 14% of women fulfilled the newly proposed ASAS MRI thresholds for active and structural SI joint lesions, respectively. BME clustered in the anterior middle joint portions at all time points, and ligamentous BME was rare. At 12 months postpartum, SPARCC erosion scores ≥3 (ASAS threshold) were observed in only 2.8% of women.At 12 months postpartum, 41% of women met the current ASAS sacroiliitis definition, which may result in false-positive assignments of axial SpA diagnosis in postpartum women with back pain. The topographical BME distribution and virtually absent erosions (ASAS threshold) at 12 months postpartum may help discriminate postpartum strain-related conditions from axial SpA-related sacroiliitis.
Females have a different metabolic response to critical illness, measured by comprehensive amino acid flux analysis
Authors: Nicolaas E.P. Deutz, Pierre Singer, Raven A. Wierzchowska-McNew, Marina V. Viana, Itai A. Ben-David, Olivier Pantet, John J. Thaden, Gabriella A.M. Ten Have, Mariëlle P.K.J. Engelen, Mette M. Berger
Journal: Metabolism (2023)
Fluctuation of Anti–Domain 1 and Anti–<scp>β<sub>2</sub>‐Glycoprotein</scp> I Antibody Titers Over Time in Patients With Persistently Positive Antiphospholipid Antibodies
Authors: Cecilia B. Chighizola, Francesca Pregnolato, Danieli Andrade, Maria Tektonidou, Vittorio Pengo, Guillermo Ruiz‐Irastorza, H. Michael Belmont, Maria Gerosa, Paul Fortin, D. Ware Branch, Laura Andreoli, Michelle A. Petri, Ricard Cervera, Jason S. Knight, Rohan Willis, Maria Efthymiou, Hannah Cohen, Doruk Erkan, Maria Laura Bertolaccini
Journal: Arthritis & Rheumatology (2023)

The present study was undertaken to longitudinally evaluate titers of antibodies against β2 -glycoprotein I (anti-β2 GPI) and domain 1 (anti-D1), to identify predictors of variations in anti-β2 GPI and anti-D1 titers, and to clarify whether antibody titer fluctuations predict thrombosis in a large international cohort of patients who were persistently positive for antiphospholipid antibodies (aPL) in the APS ACTION Registry.Patients with available blood samples from at least 4 time points (at baseline [year 1] and at years 2-4 of follow-up) were included. Detection of anti-β2 GPI and anti-D1 IgG antibodies was performed using chemiluminescence (BIO-FLASH; INOVA Diagnostics).Among 230 patients in the study cohort, anti-D1 and anti-β2 GPI titers decreased significantly over time (P < 0.0001 and P = 0.010, respectively). After adjustment for age, sex, and number of positive aPL tests, we found that the fluctuations in anti-D1 and anti-β2 GPI titer levels were associated with treatment with hydroxychloroquine (HCQ) at each time point. Treatment with HCQ, but not immunosuppressive agents, was associated with 1.3-fold and 1.4-fold decreases in anti-D1 and anti-β2 GPI titers, respectively. Incident vascular events were associated with 1.9-fold and 2.1-fold increases in anti-D1 and anti-β2 GPI titers, respectively. Anti-D1 and anti-β2 GPI titers at the time of thrombosis were lower compared to titers at other time points. A 1.6-fold decrease in anti-D1 titers and a 2-fold decrease in anti-β2 GPI titers conferred odds ratios for incident thrombosis of 6.0 (95% confidence interval [95% CI] 0.62-59.3) and 9.4 (95% CI 1.1-80.2), respectively.Treatment with HCQ and incident vascular events in aPL-positive patients predicted significant anti-D1 and anti-β2 GPI titer fluctuations over time. Both anti-D1 and anti-β2 GPI titers decreased around the time of thrombosis, with potential clinical relevance.
Reduction of Proinflammatory Effector Functions Through Remodeling of Fatty Acid Metabolism in <scp>CD8</scp>+ T Cells From Rheumatoid Arthritis Patients
Authors: Franziska V. Kraus, Simon Keck, Karel D. Klika, Jürgen Graf, Rui A. Carvalho, Hanns‐Martin Lorenz, M. Margarida Souto‐Carneiro
Journal: Arthritis & Rheumatology (2023)

Rheumatoid arthritis (RA) CD8+ T cells maintain their effector proinflammatory phenotype by changing their metabolism toward aerobic glycolysis. However, their massive energy and biosynthesis needs may require additional substrates other than glucose. Since systemic alterations in lipid metabolism have been reported in RA patients, we explored the role of fatty acid (FA) metabolism in CD8+ T cells to identify potential targets to curb their proinflammatory potential.The expression of FA metabolism-related genes was analyzed for total CD8+ T cells and CD8+ T cell subsets in the data of RA patients and healthy controls retrieved from the GEO database. Functional assays were performed using peripheral blood CD8+ T cells isolated from RA (n = 31), psoriatic arthritis (n = 26), and spondyloarthritis (n = 21) patients receiving different therapies (disease-modifying antirheumatic drugs, biologics, and JAK inhibitors) and from healthy controls (n = 14). We quantified the expression of FA transporters, lipid uptake, intracellular FA content, cytokine production, activation, proliferation, and capacity to inhibit tumor cell growth, either with or without FA metabolism inhibitors.The CD8+ T cell gene expression profile of FA metabolism-related genes was significantly different between untreated RA patients and healthy controls. RA patients who had a good clinical response after 6 months of methotrexate therapy had significantly increased expression of FA metabolism-related genes. Cell surface expression of the FA transporters FA binding protein 4 (FABP4) and G protein-coupled receptor 84 (GPR84) and FA uptake were higher in effector and memory CD8+ T cells from RA patients compared to those from healthy controls. In vitro blockade of FA metabolism significantly impaired CD8+ T cell effector functions.RA CD8+ T cells present an altered FA metabolism, which could provide potential therapeutic targets to control their proinflammatory profile, particularly therapies directed against the transport and oxidation of free FA.
Association of Dipeptidylpeptidase 4 (<scp>CD26</scp>) With Chondrocyte Senescence and Radiographic Progression in Knee Osteoarthritis
Authors: Yu‐Hsiu Chen, Xin Zhang, Ching‐Heng Chou, Ming‐Feng Hsueh, David Attarian, Yi‐Ju Li, Virginia Byers Kraus
Journal: Arthritis & Rheumatology (2023)

To evaluate the association of dipeptidylpeptidase 4 (DPP-4; also known as CD26) with cellular senescence of human cartilage and progression of knee osteoarthritis (OA).
The 5th edition of the WHO classification of haematolymphoid tumors: comments from the Groupe Francophone de Cytogénétique Hématologique (GFCH)
Authors: Florence Nguyen-Khac, Audrey Bidet, Marie-Bérengère Troadec, Lauren Veronese, Nathalie Auger, Agnes Daudignon, Nathalie Nadal, Dominique Penther, Lucienne Michaux, Marina Lafage-Pochitaloff, Christine Lefebvre
Journal: Leukemia (2023)